Synthesis, characterization and augmented anticancer potential of PEG-betulinic acid conjugate

Autor: Ravindra Dhar Dubey, P. L. Sangwan, Ankit Saneja, Dilip M. Mondhe, Sheikh Abdullah Tasaduq, Mubashir Javed Mintoo, Love Sharma, Amit Kumar, Prem N. Gupta, Gurdarshan Singh, Amrinder Singh
Rok vydání: 2016
Předmět:
Male
Carboxylic acid
Proton Magnetic Resonance Spectroscopy
Blotting
Western
Bioengineering
02 engineering and technology
Polyethylene glycol
Hemolysis
Ehrlich ascites carcinoma
Polyethylene Glycols
Biomaterials
03 medical and health sciences
chemistry.chemical_compound
Inhibitory Concentration 50
Mice
0302 clinical medicine
Drug Stability
In vivo
Betulinic acid
Cell Line
Tumor
PEG ratio
Spectroscopy
Fourier Transform Infrared
Animals
Humans
Carbon-13 Magnetic Resonance Spectroscopy
Rats
Wistar
Betulinic Acid
Cytotoxicity
Carcinoma
Ehrlich Tumor
chemistry.chemical_classification
Cell Death
Chemistry
021001 nanoscience & nanotechnology
Antineoplastic Agents
Phytogenic
Triterpenes
Biochemistry
Solubility
Mechanics of Materials
030220 oncology & carcinogenesis
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
0210 nano-technology
Pentacyclic Triterpenes
Biomarkers
Conjugate
Subcellular Fractions
Zdroj: Materials scienceengineering. C, Materials for biological applications. 73
ISSN: 1873-0191
Popis: Betulinic acid (BA), a pentacyclic lupine-type triterpene, is reported to inhibit cell growth in a variety of cancers. However, its efficacy is limited by its poor aqueous solubility and relatively short half-life. In this study, BA-monomethoxy polyethylene glycol (mPEG) conjugate was synthesized by covalent coupling the C-28 carboxylic acid position of BA with amine groups of mPEG, in order to improve its solubility and anticancer efficacy. mPEG-BA conjugate was characterized using various analytical techniques including NMR, FT-IR and MALDI-MS. The mPEG-BA conjugate was cytotoxic, demonstrated internalization and induced cell apoptosis in Hep3B and Huh7 hepatic cancer cells. The western-blot analysis revealed, marked decrease in Bcl-2/Bax ratio, and increase in cleaved-PARP and cleaved-caspase-3 expressions. In vivo studies in Ehrlich ascites tumor (EAT) model following intravenous administration demonstrated significant reduction in tumor volume in case of PEGylated BA as compare to native BA. Furthermore, PEGylated BA treated EAT mice showed no biochemical and histological toxicities. These findings demonstrate the potential of PEGylated BA in cancer therapy, with improved water solubility and efficacy.
Databáze: OpenAIRE
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